A Unique Mouse Model of Early Life Exercise Enables Hippocampal Memory and Synaptic Plasticity

Ivy, Autumn S; Yu, Tim; Kramár, Enikö A.; Parievsky, Sonia; Sohn, Fred; Vu, Thao

doi:10.1038/s41598-020-66116-4

Cited by 24 publications

(29 citation statements)

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“…Evidence from animal studies also supports that exercise can enhance brain plasticity. Moderate-intensity aerobic exercise promotes the proliferation and survival of neurons in the hippocampus and cortex, increased BDNF and dendrites, and improves spatial learning and memory in rodents ( Serra et al, 2019 ; Ivy et al, 2020 ). Another study also reported that moderate-intensity swimming training could ameliorate the anxiety-like behavior of mice by increasing proteins that play a key role in hippocampal plasticity, such as growth-associated protein 43, synaptophysin, and BDNF ( Liu et al, 2018 ).…”

Section: Main Textmentioning

confidence: 99%

Lactate as Potential Mediators for Exercise-Induced Positive Effects on Neuroplasticity and Cerebrovascular Plasticity

et al. 2021

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The accumulated evidence from animal and human studies supports that exercise is beneficial to physical health. Exercise can upregulate various neurotrophic factors, activate neuroplasticity, and play a positive role in improving and enhancing cerebrovascular function. Due to its economy, convenience, and ability to prevent or ameliorate various aging-related diseases, exercise, a healthy lifestyle, is increasingly popularized by people. However, the mechanism by which exercise performs this function and how it is transmitted from muscles to the brain remains incompletely understood. Here, we review the beneficial effects of exercise with different intensities on the brain with a focus on the positive effects of lactate on neuroplasticity and cerebrovascular plasticity. Based on these recent studies, we propose that lactate, a waste previously misunderstood as a by-product of glycolysis in the past, may be a key signal molecule that regulates the beneficial adaptation of the brain caused by exercise. Importantly, we speculate that a central protective mechanism may underlie the cognitive benefits induced by exercise.

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Section: Main Textmentioning

confidence: 99%

Lactate as Potential Mediators for Exercise-Induced Positive Effects on Neuroplasticity and Cerebrovascular Plasticity

et al. 2021

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“…Aerobic exercise has generally been found to enhance performance on cognitive tasks involving the hippocampus in both adult humans and animal models 15,16 . The type, timing, and duration of exercise exposure matters with regard to whether it has a persistent impact on hippocampal function [17][18][19] . However, in general, the effects of exercise on hippocampal memory in adulthood are transient [17][18][19] .…”

Section: Introductionmentioning

confidence: 99%

“…The type, timing, and duration of exercise exposure matters with regard to whether it has a persistent impact on hippocampal function [17][18][19] . However, in general, the effects of exercise on hippocampal memory in adulthood are transient [17][18][19] . Findings in adult rodents also implicate a role for histone modifying enzymes in the mechanisms of exerciseinduced benefits to hippocampal memory.…”

Section: Introductionmentioning

confidence: 99%

“…This suggests a "molecular memory" of the initial exercise 23 . Although the majority of these studies have been performed in adults, more recent work suggests that the effects of exercise on hippocampal memory and the associated alterations in neurotrophic factor expression, synaptic plasticity, and neurogenesis are similar in juvenile and adolescent periods 17,[24][25][26][27] . Previous work in our lab showed that early-life exercise (ELE) for either one week (juvenile period; postnatal days (P) [21][22][23][24][25][26][27] or three weeks (juvenile-adolescence; P21-41) facilitated hippocampal long-term memory formation in response to a learning stimulus typically insufficient for forming long-term memory.…”

Section: Introductionmentioning

confidence: 99%

“…Previous work in our lab showed that early-life exercise (ELE) for either one week (juvenile period; postnatal days (P) [21][22][23][24][25][26][27] or three weeks (juvenile-adolescence; P21-41) facilitated hippocampal long-term memory formation in response to a learning stimulus typically insufficient for forming long-term memory. This finding was associated with increased long-term potentiation (LTP) as well as modulations to synaptic physiology in hippocampal CA1 17 . Notably, the hippocampal memory effects of juvenile ELE during P21-27 persisted two weeks after exercise cessation, which is longer than the effect of exercise on adult hippocampal function 23 .…”

Section: Introductionmentioning

confidence: 99%

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Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation

Raus

Fuller

Nelson

et al. 2021

Preprint

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Aerobic exercise promotes physiological and molecular adaptations in neurons to influence brain function and behavior. The most well studied neurobiological consequences of exercise are those which underlie exercise-induced improvements in hippocampal memory, including the expression and regulation of the neurotrophic factor Bdnf. Whether aerobic exercise taking place during early-life periods of postnatal brain maturation has similar impacts on gene expression and its regulation remains to be investigated. Using unbiased next-generation sequencing we characterize gene expression programs and their regulation by specific, memory-associated histone modifications during juvenile-adolescent voluntary exercise (ELE). Traditional transcriptomic and epigenomic sequencing approaches have either used heterogeneous cell populations from whole tissue homogenates or flow cytometry for single cell isolation to distinguish cell types / subtypes. These methods fall short in providing cell-type specificity without compromising sequencing depth or procedure-induced changes to cellular phenotype. In this study, we use simultaneous isolation of translating mRNA and nuclear chromatin from a neuron-enriched cell population to more accurately pair ELE-induced changes in gene expression with epigenetic modifications. We employ a line of transgenic mice expressing the NuTRAP (Nuclear Tagging and Translating Ribosome Affinity Purification) cassette under the Emx1 promoter allowing for brain cell-type specificity. We then developed a technique that combines nuclear isolation using Isolation of Nuclei TAgged in Specific Cell Types (INTACT) with Translating Ribosomal Affinity Purification (TRAP) methods to determine cell type-specific epigenetic modifications influencing gene expression programs from a population of Emx1 expressing hippocampal neurons. Data from RNA-seq and CUT&RUN-seq were coupled to evaluate histone modifications influencing the expression of translating mRNA in neurons after early-life exercise (ELE). We also performed separate INTACT and TRAP isolations for validation of our protocol and demonstrate similar molecular functions and biological processes implicated by gene ontology (GO) analysis. Finally, as prior studies use tissue from opposite brain hemispheres to pair transcriptomic and epigenomic data from the same rodent, we take a bioinformatics approach to compare hemispheric differences in gene expression programs and histone modifications altered by by ELE. Our data reveal transcriptional and epigenetic signatures of ELE exposure and identify novel candidate gene-histone modification interactions for further investigation. Importantly, our novel approach of combined INTACT/TRAP methods from the same cell suspension allows for simultaneous transcriptomic and epigenomic sequencing in a cell-type specific manner.

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Treadmill exercise prevents recognition memory impairment in VD rat model and enhancement of hippocampal structural synaptic plasticity

Zhang,

Wu,

Fan

et al. 2024

Brain and Behavior

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ObjectiveIn vascular dementia (VD), memory impairment caused by the damage of synaptic plasticity is the most prominent feature that afflicts patients and their families. Treadmill exercise has proven beneficial for memory by enhancing synaptic plasticity in animal models including stroke, dementia, and mental disorders. The aim of this study was to examine the effects of treadmill exercise on recognition memory and structural synaptic plasticity in VD rat model.MethodsMale Sprague‐Dawley rats were randomly assigned into four groups: control group (C group, n = 6), vascular dementia group (VD group, n = 6), treadmill exercise and vascular dementia group (Exe‐VD group, n = 6), and treadmill exercise group (Exe group, n = 6). Four‐week treadmill exercise was performed in the Exe‐VD and Exe groups. Then, the common carotid arteries of rats in the VD and Exe‐VD groups were identified to establish the VD model. Behavior tests (open‐field test and novel recognition memory test) were adopted to evaluate anxiety‐like behavior and recognition memory. Transmission electron microscopy and Golgi staining were performed to observe synaptic ultrastructure and spine density in the hippocampus.ResultsOur study demonstrated that VD rat exhibited significantly anxiety‐like behavior and recognition impairment (p < .01), while treadmill exercise significantly alleviated anxiety‐like behavior and improved recognition memory in VD rat (p < .01). Transmission electron microscopy revealed that hippocampal synapse numbers were significantly decreased in the VD group compared to the control group (p < .05). These alterations were reversed by treadmill exercise, and the rats exhibited healthier synaptic ultrastructure, including significantly increased synapse (p < .05). Meanwhile, golgi staining revealed that the spine numbers of the hippocampus were significantly decreased in the VD group compared to the control group (p < .05). When compared with the VD group, hippocampal spine numbers were significantly increased in the Exe‐VD group (p < .05).ConclusionThe improvement of VD‐associated recognition memory by treadmill exercises is associated with enhanced structural synaptic plasticity in VD rat model.

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A Unique Mouse Model of Early Life Exercise Enables Hippocampal Memory and Synaptic Plasticity

Cited by 24 publications

References 65 publications

Lactate as Potential Mediators for Exercise-Induced Positive Effects on Neuroplasticity and Cerebrovascular Plasticity

Lactate as Potential Mediators for Exercise-Induced Positive Effects on Neuroplasticity and Cerebrovascular Plasticity

Early life exercise primes the neural epigenome to facilitate gene expression and hippocampal memory consolidation

Treadmill exercise prevents recognition memory impairment in VD rat model and enhancement of hippocampal structural synaptic plasticity

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